Abstract:
Background Long-term exposure to air pollution affects blood lipids, but the exact molecular biological mechanism is not yet clear.
Objective This study explores a potential mediation effect of DNA methylation on the relationship between one-year average exposure to air pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) and blood lipid levels in population at high risk for cardiovascular disease.
Methods A total of 176 cases were selected from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project across 61 cities in 15 provinces of China's mainland. The blood levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and other biochemical indicators were measured. Meanwhile, based on the data of one-year average exposure to air pollutants and of genome-wide methylation chips (EPIC 850 k) obtained from previous projects, causal inference test (CIT) method was employed to identify DNA methylation sites that exhibit a mediation effect on the relationship between air pollutant exposure and lipid levels.
Results Only NO2 exposure (per 10 μg·m-3 increase) was associated with elevated levels of TC (b=0.259, Sb=0.084, P=0.002), LDL-C (b=0.173, Sb=0.059, P=0.004), and non-HDL-C (nHDL-C) (b=0.227, Sb=0.082, P=0.006) after adjustment for age, gender, body mass index (BMI), current smoking, drinking, hypertension, and diabetes, while other air pollutants (SO2, PM10, PM2.5, O3, and CO) were not (P>0.05). The CIT analysis results showed that there were 2 methylation sites (without annotation genes), 16 methylation sites (11 sites with annotation genes), and 32 methylation sites (23 sites with annotation genes) mediating the association between increased NO2 pollutant exposure and elevated levels of TC, LDL-C, and nHDL-C (P1 < 0.05, P2 < 0.05, P3 < 0.05, P4>0.05) among the included 5 615 methylation loci related with NO2 exposure (P < 0.01), respectively.
Conclusion DNA methylation at specific sites caused by long-term NO2 exposure is correlated with elevated levels of TC, LDL-C, and nHDL-C.